Abstract

Endo180, also known as uPAR associated protein (uPARAP), is a member of the tri-molecular complex formed by uPA along with uPAR in the endocytic processing of collagen degradation. In the present study, we found that this membrane-bound protein was released into culture supernates of meningioma and other cancer cell types. In addition, we report a tremendous increase of Endo180 transcript and protein levels in irradiated meningioma cells and their culture filtrates. While non-denaturing immunoprecipitation studies suggested that Endo180 interacts with uPA in cell-free conditions, uPA binding was significantly quenched by deglycosylation of solubilized Endo180. Myc-tagged cDNA expression suggested shedding of Endo180 against secretion from meningioma cells. Function blocking and knockdown of Endo180 adversely affected the proliferation of meningioma cells with concomitant decrease in uPA activity and uPAR expression. We also observed a significant rise of Endo180 expression in meningioma clinical samples and tumors in animal models. A further increase of expression was observed among the brain sections of mice infused with irradiated meningioma cells. Taken together, our results demonstrate that solubilization of Endo180 characterizes a different hierarchy of endocytic receptor functioning in meningioma.